Stochastic modeling of ovarian tissue cryopreservation and transplantation

Cryopreservation and transplantation of ovarian tissue is an important fertility preservation strategy for patients at risk of premature ovarian failure due to gonadotoxic treatments such as chemotherapy or radiation therapy for cancer patients. It is currently the only option available for prepubertal girls and for patients who must begin treatment immediately and cannot undergo ovarian stimulation. However, the precise microscopic mechanisms of the processes that occur in the preservation and transplantation of ovarian tissue are not yet understood. It is also unclear how to control the procedure to achieve the most optimal health and fertility outcomes. In this study, we developed a novel theoretical method to investigate if there are optimal conditions for ovarian tissue cryopreservation and transplantation to maximize long-term ovarian function and health. For a fixed tissue removal age, our stochastic follicle depletion model predicts that menopause might come earlier, at the same time, or later in comparison with the case without tissue removal and retransplantation. The outcome depends on the grafting fraction, its survival after retransplantation, and the time of ovarian tissue return. Since the reproductive quality of follicles decreases with age, it is also argued that there is an optimal time of retransplantation that should maximize the probability of fertility. Mechanistic explanations of the observed phenomena are also presented, providing more microscopic insights on the molecular picture of complex ovarian biological processes.